Lecture 2 Receptors Flashcards
Role of a drug
Interferes with messaging where a chemical is detected on a receptor of more downstream. Interfering with the receptor itself gives more specificity
what is an agonist?
a molecule that switches on signalling by receptor and selective for a particle receptor if concentrations are controlled
what is an antagonist?
a molecule that binds to a receptor to make it unresponsive and can be used to treat an overdose
similarity in receptor families
has the same number of transmembrane domains
Ligand-gated ion channels
- Aqueous pore for ions to flow through
- P loop lines aqueous pore
- normally 4-5 proteins come together to form channel
- Example is a nicotinic receptor (nAChR)
G - protein coupled receptors
- has a 7 transmembrane domain structure
- signal change by activation of G protein
- made up of 3 subunits (alpha,beta and gamma)
- cannabis works by GPCR
Canonical signalling
when an agonist binds to receptor there is a rearrangement of the protein
‘Canonical’ signalling by GPCRs
- alpha subunit has association with GDP
- once agonist is bound, causes a change in alpha subunit and has a higher affinity for GTP
- Once associated with GTP, alpha subunit comes off the receptor and controls action of target proteins.
- GTP loses a phosphate to become GDP associating with alpha subunit to terminate signalling.
Kinase receptors
- Has one kinase domain
- attracts enzyme with tyrosine kinase to cause phosphorylation
- commonly leads to changes in transcription
- Cytokines are kinase linked
- insulin receptors are kinase linked
Nuclear receptors
- No transmembrane domains
- has DNA binding site and directly binds to DNA
- found inside the cell and moves into nucleus when agonist is bound.
- ligand must be able to cross plasma membrane (lipophilic)
- target for steroids
class 1 nuclear receptors
these are homodimeric
class 2 nuclear receptors
- already in the nucleus
- have a heterodimeric structure, formed from two different proteins
